Test Catalog

Test Id : HPGLP

Hereditary Paraganglioma/Pheochromocytoma Panel, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation for patients with a personal or family history suggestive of a hereditary paraganglioma and pheochromocytoma (PGL/PCC) syndrome

 

Establishing a diagnosis of a hereditary PGL/PCC, allowing for targeted surveillance based on associated risks

 

Identifying genetic variants associated with increased risk for PGL/PCC, allowing for predictive testing and appropriate screening of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 11 genes associated with hereditary paraganglioma and/or pheochromocytoma: FH, MAX, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL. For more information see Method Description, Targeted Genes and Methodology Details for Hereditary Paraganglioma/Pheochromocytoma Panel in Special Instructions.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary paraganglioma/pheochromocytoma (PGL/PCC).

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Hereditary PGL/PCC Panel

Aliases
Lists additional common names for a test, as an aid in searching

Paraganglioma-pheochromocytoma panel

Hereditary paraganglioma-pheochromocytoma panel

Paraganglioma

Pheochromocytoma

PGL

PCC

HPGP

Von Hippel Lindau syndrome (VHL)

(VHL) Von Hippel Lindau

Multiple endocrine neoplasia type 2

MEN2

Neurofibromatosis type 1

NextGen Sequencing Test

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Customization of this panel or single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

 

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. For more information see FMTT / Familial Mutation, Targeted Testing, Varies.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Inherited Cancer Syndromes Patient Information Sheet (T519) in Special Instructions

3. Targeted Genes and Methodology Details for Hereditary Paraganglioma/Pheochromocytoma in Special Instructions

4. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.

 

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation for patients with a personal or family history suggestive of a hereditary paraganglioma and pheochromocytoma (PGL/PCC) syndrome

 

Establishing a diagnosis of a hereditary PGL/PCC, allowing for targeted surveillance based on associated risks

 

Identifying genetic variants associated with increased risk for PGL/PCC, allowing for predictive testing and appropriate screening of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 11 genes associated with hereditary paraganglioma and/or pheochromocytoma: FH, MAX, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL. For more information see Method Description, Targeted Genes and Methodology Details for Hereditary Paraganglioma/Pheochromocytoma Panel in Special Instructions.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary paraganglioma/pheochromocytoma (PGL/PCC).

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Paragangliomas and pheochromocytomas are rare neuroendocrine tumors that arise from autonomous ganglia. Tumors located within the adrenal medulla (the largest sympathetic ganglion) are called pheochromocytomas (PCC), while those that stem from either parasympathetic or sympathetic ganglia are designated paragangliomas (PGL).

 

PGL/PCC have a germline genetic basis in up to 30% of cases.(1) The genes implicated in hereditary PGL/PCC syndrome include MAX, TMEM127, FH and the SDHx.

 

The genes most commonly associated with hereditary PGL/PCC syndromes are the succinate dehydrogenase-associated genes SDHA, SDHAF2, SDHB, SDHC and SDHD.

 

Germline alterations in the MAX gene are typically associated with increased risk for PCC, although some individuals have been identified with PGL. MAX variants occur in approximately 1% of patients with hereditary PGL/PCC syndromes.(2)

 

TMEM127 variants are associated most commonly with PCC and rarely PGL.(1) Alterations of TMEM127 account for approximately 2% of individuals with hereditary PGL/PCC.(2)

 

Recent evidence suggests that pathogenic variants in FH also increased risk for PGL/PCC.(3,4) Individuals with pathogenic FH variants also carry a significantly increased risk for cutaneous or uterine leiomyomata and renal tumors.(5)

 

Alterations in VHL, NF1, and RET also increase risk for PGL/PCC in addition to other types of tumors.(6)

 

Pathogenic variants in the VHL gene are associated with a syndrome called von Hippel Lindau (VHL) syndrome. In addition to PGL/PCC, individuals with VHL are also at increased risk for hemangioblastomas, renal cell carcinoma, pancreatic cysts, neuroendocrine tumors, endolymphatic sac and epididymal tumors.(7)

 

NF1 gene variants are associated with neurofibromatosis type I (NF1). Individuals with NF1 are at increased risk for pheochromocytomas in addition to neurofibromas and central nervous system gliomas, such as optic nerve gliomas. NF1 is also characterized by other features such as cafe-au lait macules, axillary/inguinal freckling and Lisch nodules.(8)

 

Pathogenic RET variants result in a syndrome called multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid cancer (FMTC). In addition to an increased risk for PGL/PCC, individuals with MEN2/FMTC also have a very high risk to develop medullary thyroid cancer. Individuals with MEN2 may also have other features such as primary hyperparathyroidism, mucosal neuromas, ganglioneuromatosis and distinctive facial features.(9)

 

The National Comprehensive Cancer Network and the American Cancer Society provide recommendations regarding the medical management of individuals with hereditary PGL/PCC syndromes.(10)

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected variants are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(11) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of further testing options, or for assistance in the interpretation of these results, Mayo Clinic Laboratory genetic counselors can be contacted at 800-533-1710.

 

Technical Limitations
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Insertions/deletions (indels) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller indels.

 

Deletion/Duplication Analysis

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Genes may be added or removed based on updated clinical relevance. For the most up to date list of genes included in this test or detailed information regarding gene specific performance and technical limitations, see Method Description, Targeted Genes and Methodology Details for Hereditary Paraganglioma/Pheochromocytoma in Special Instructions or contact a laboratory genetic counselor at 800-533-1710.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants
At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.

 

Variant Evaluation

Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline. Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgement.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Else T, Greenberg S, Fishbein L: Hereditary paraganglioma-pheochromocytoma syndromes. GeneReviews [Internet]. University of Washington, Seattle; 2008. Updated October 4, 2018. Accessed July 6, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1548/

2. Bausch B, Schiavi F, Ni Y, et al: European-American-Asian Pheochromocytoma-Paraganglioma Registry Study Group. Clinical characterization of the pheochromocytoma and paraganglioma susceptibility genes SDHA, TMEM127, MAX, and SDHAF2 for gene-informed prevention. JAMA Oncol. 2017 Sep 1;3(9):1204-1212

3. Udager AM, Magers MJ, Goerke DM, et al: The utility of SDHB and FH immunohistochemistry in patients evaluated for hereditary paraganglioma-pheochromocytoma syndromes. Hum Pathol. 2018 Jan;71:47-54

4. Castro-Vega LJ, Buffet A, De Cubas AA, et al: Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet. 2014 May 1;23(9):2440-2446

5. Kamihara J, Schultz KA, Rana HQ: FH tumor predisposition syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated August 13, 2020. Accessed July 6, 2021 Available at www.ncbi.nlm.nih.gov/books/NBK1252/

6. Shah MH, Goldner WS, Halfdanarson TR et al: NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018. J Natl Compr Canc Netw. 2018 Jun;16(6):693-702

7. van Leeuwaarde RS, Ahmad S, Links TP, et al: Von Hippel-Lindau syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated September 6, 2018. Accessed July 6, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1463/

8. Friedman JM: Neurofibromatosis 1. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1998. Updated June 6, 2019. Accessed July 6, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1109/

9. Eng C: Multiple Endocrine Neoplasia Type 2. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1999. Updated August 15, 2019. Accessed July 6, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1257/

10. Benn DE, Gimenez-Roqueplo AP, Reilly JR, et al: Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab. 2006 Mar;91(3):827-836

11. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known pathogenic variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for insertions/deletions (indels) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed. For details regarding the targeted genes analyzed for each test see Targeted Genes and Methodology Details for Hereditary Paraganglioma/Pheochromocytoma in Special Instructions.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. For details regarding the specific gene regions not routinely covered see Targeted Genes and Methodology Details for Hereditary Paraganglioma/Pheochromocytoma in Special Instructions.

 

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.(Unpublished Mayo method)

 

Genes analyzed: FH, MAX, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

Supplemental

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 4 weeks

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81437

LOINC® Information

Test Id Test Order Name Order LOINC Value
HPGLP Hereditary PGL/PCC Panel In Process
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
614731 Test Description 62364-5
614732 Specimen 31208-2
614733 Source 31208-2
614734 Result Summary 50397-9
614735 Result 82939-0
614736 Interpretation 69047-9
614737 Resources In Process
614738 Additional Information 48767-8
614739 Method 85069-3
614740 Genes Analyzed 48018-6
614741 Disclaimer 62364-5
614742 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports